A clinical comparison of topical piroxicam and EMLA cream for pain relief and inflammation in laser hair removal.
The aim of this study was to compare the efficacy of topical piroxicam and EMLA cream on pain control and subsequent inflammation in neodymium:yttrium-aluminum-garnet (Nd:YAG) 1,064 nm laser hair removal in female volunteers. Fifty female volunteers were enrolled in this prospective, randomized, double-blind, clinical study over a 6-month period. Patients were randomly assigned to receive topical piroxicam as group Piroxicam or EMLA cream as group EMLA. Topical analgesics were applied to the treatment sites for 60 min. The pain scores [on a visual analog scale (VAS)] and side effects were recorded before the hair removal, during the hair removal, at the end of the hair removal, and 1 h, 2 h and 24 h after the hair removal. Patients' characteristics and the treatment settings of the Nd:YAG 1,064 nm laser were similar in the two groups. The pain scores (VAS) were similar, and satisfaction was high in both groups after the hair removal. The number of blanching and erythema episodes were significantly higher in group E than in group P (P < 0.001). Inflammatory side effects were less frequent in group P than in group E after the procedure (P < 0.001). This study showed that topical piroxicam and EMLA provided adequate and similar pain relief after Nd:YAG 1,064 nm laser hair removal in female volunteers. Topical piroxicam was associated with fewer inflammatory side effects than was EMLA cream, because of its anti-inflammatory effect after the procedure.


Improving nursing home staff knowledge and attitudes about pain.
Effective pain management remains a serious problem in the nursing home setting. Barriers to achieving optimal pain practices include staff knowledge deficits, biases, and attitudes that influence assessment and management of the residents' pain. Twelve nursing homes participated in this intervention study: six treatment homes and six control homes, divided evenly between urban and rural locations. Three hundred licensed and unlicensed nursing home staff members completed written knowledge and attitude surveys at baseline, and 378 staff members completed the surveys after intervention implementation. Baseline results revealed notable knowledge deficits in the areas of pharmacology, drug addiction and dependence, side effect management, and nonpharmacologic management-strategy effectiveness. Significant differences were noted by job title (registered nurse/licensed practical nurse/certified nursing assistant). Case studies displayed a knowledge application problem, with nurses often filtering resident pain reports through observed resident behaviors. The intervention led to significant improvement in knowledge scores in some, but not all, the treatment homes. Perceived barriers to effective pain management showed a significant decline across all study nursing homes. Knowledge deficits related to pain management persist in nursing homes. An interactive multifaceted educational program was only partially successful in improving knowledge across settings and job categories. Attitudes and beliefs appear more difficult to change, whereas environmental and contextual factors appeared to be reducing perceived barriers to effective pain management across all participating nursing homes.


Ten years of respiratory cytopathology at Duke University Medical Center. III. The significance of inconclusive cytopathologic diagnoses during the years 1970 to 1974.
This paper reports on the significance of inconclusive cytopathologic diagnoses made on cytologic specimens from the lower respiratory tract of patients seen at the Duke University Medical Center during the years 1970 to 1974. During that period, a total of 9,892 cytopathologic specimens from the lower respiratory tract were processed. Conclusive cytopathologic diagnoses of cancer were made in 363 patients. In 218 additional patients, one or more inconclusive cytopathologic diagnoses were made. In 70 patients, a cytopathologic diagnosis of atypical metaplasia was made. In 28 of these 70 patients (40% of the group), this diagnosis was followed by a tissue confirmation of cancer. In the remaining 42 patients (60%), the follow-up studies revealed the presence of a variety of nonneoplastic diseases, usually inflammatory in origin. In these patients, various types of pneumonias constituted the most frequent type of disease. Another 135 patients had originally been given a cytopathologic diagnosis of "atypical cells suspicious for malignancy." In 92 (approximately 68%) of these patients, this suspicion of cancer was confirmed by tissue. In 43 patients (approximately 32%) no cancer was found. In this latter group of patients, the most common underlying disease process was also pneumonia.


Quantitative Metabolic Volumetric Product on 18Fluorine-2fluoro-2-deoxy-D-glucose-positron Emission Tomography/Computed Tomography in Assessing Treatment Response to Disease-modifying Antirheumatic Drugs in Rheumatoid Arthritis: Multiparametric Analysis Integrating American College of Rheumatology/European League Against Rheumatism Criteria.
The purpose of this study was to assess the role of fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in the evaluation of treatment response evaluation to disease-modifying antirheumatic drug (DMARD) therapy in patients of rheumatoid arthritis (RA). A total of ten patients with proven diagnosis of RA as per the 2010 American College of Rheumatology/European League against Rheumatism (EULAR) criteria were prospectively evaluated. All patients underwent clinical and biochemical evaluation and a baseline FDG-PET/CT with assessment of maximum standardized uptake value and metabolic volumetric product (MVP) values. DMARD therapy was started with a combination of hydroxychloroquine and sulfasalazine. On follow-up at 3 and 6 months, the response to treatment was assessed by clinical, biochemical, and FDG-PET/CT parameters. These parameters were analyzed in a combined manner, and the patients were grouped into 4 categories as per response to DMARD therapy - complete response, good response, mixed response, and no response. Evaluation of treatment response in ten patients at 3rd month and in nine patients at 6 months showed (a) agreement for MVP, biochemical parameters with clinical symptomatic assessment in all patients, (b) while agreement for EULAR score was noted in only three patients and disagreement in seven patients with clinical symptoms Response EULAR (rEULAR) (0.37) and at 6 months in only three patients and disagreement in six patients, rEULAR (0.52). The correlation factors at 3rd month and 6th months were, respectively, as follows: rMVP (0.67 and 0.75), response RA factor (0.54 and 0.74), response erythrocyte sedimentation rate (0.81 and 0.73), response C-reactive protein (0.78 and 0.51), and response anti-cyclic citrullinated peptide antibodies (0.33 and 0.54). The overall response to DMARD therapy at 3 months was assessed with results showing good response by four cases (40%), mixed response by 1 (10%), no response by 5 (50%), and complete response by none (0%). Step-up therapy at 3 months was initiated in four patients showing nonresponse/progression on clinical symptomatic assessment; of these, two patients showed a good response, one mixed response, and the remaining one continued to show nonresponse at 6 months follow-up. One patient who had a minimal response at 3 months on PET-CT (only 5.96% reduction of MVP) was continued on the same DMARD in view of clinical symptomatic good response (at 3 months) but ultimately had disease progression in all scales and worsening of symptom (at 6 months). FDG-PET/CT-based assessment of inflammatory activity noted in the joints of RA with quantitative parameters can be a promising approach for the whole body assessment of RA disease activity and treatment response assessment, especially in inconclusive cases and correlates well with other parameters. MVP can be used as a useful objective and adjunct parameter for assessing response to treatment.


Diabetes-induced vascular dysfunction in the retina: role of endothelins.
Vasoactive factors like endothelins, by virtue of the microvascular regulation as well as by other effects, possibly play important parts in the pathogenesis of diabetic retinal microangiopathy. We investigated retinal vascular dysfunction in streptozotocin-induced diabetes and its relation with endothelins in short- and long-term diabetes. Diabetic rats with or without an endothelin receptor antagonist (bosentan) treatment were investigated after 1 month and 6 months of follow-up. Retinal blood flow was measured and compared with age- and sex-matched non-diabetic control animals. Retinal tissues were analysed for endothelin-1, endothelin-3, endothelin A and endothelin B mRNA. Distribution of endothelin-1 and endothelin-3 was investigated by immunocytochemistry and that for endothelin receptors by ligand binding and autoradiography. Diabetic animals showed hyperglycaemia, glycosuria, elevated glycated haemoglobin values and reduced body weight gain. Retinal blood flow showed an increased resistivity index, an indicator of vasoconstriction, after 1 month of diabetes which was prevented by treatment with bosentan. This functional change in diabetes was eliminated after 6 months of follow-up. The retina from the diabetic animals showed increased mRNA expression for endothelin-1, endothelin-3 and endothelin A after one month. In addition, endothelin B mRNA expression was increased after 6 months. Furthermore, endothelin-1 and endothelin-3 immunoreactivity and endothelin receptor concentrations were increased in the retina of diabetic rats. The results from this study indicate that the endothelin system is of importance in mediating retinal changes in diabetes although mechanisms of the endothelin system alteration as well as their effects might vary depending on the duration of diabetes. [Diabetologia (1999) 42: 1228-1234]


Multicenter Evaluation of a PCR-Based Digital Microfluidics and Electrochemical Detection System for the Rapid Identification of 15 Fungal Pathogens Directly from Positive Blood Cultures.
Routine identification of fungal pathogens from positive blood cultures by culture-based methods can be time-consuming, delaying treatment with appropriate antifungal agents. The GenMark Dx ePlex investigational use only blood culture identification fungal pathogen panel (BCID-FP) rapidly detects 15 fungal targets simultaneously in blood culture samples positive for fungi by Gram staining. We aimed to determine the performance of the BCID-FP in a multicenter clinical study. Blood culture samples collected at 10 United States sites and tested with BCID-FP at 4 sites were compared to the standard-of-care microbiological and biochemical techniques, fluorescence in situ hybridization using peptide nucleic acid probes (PNA-FISH) and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Discrepant results were analyzed by bi-directional PCR/sequencing of residual blood culture samples. A total of 866 clinical samples, 120 retrospectively and 21 prospectively collected, along with 725 contrived samples were evaluated. Sensitivity and specificity of detection of Candida species (C. albicans, C. auris, C. dubliniensis, C. famata, C. glabrata, C. guilliermondii, C. kefyr, C. krusei, C. lusitaniae, C. parapsilosis, and C. tropicalis) ranged from 97.1 to 100% and 99.8 to 100%, respectively. For the other organism targets, sensitivity and specificity were as follows: 100% each for Cryptococcus neoformans and C. gattii, 98.6% and 100% for Fusarium spp., and 96.2% and 99.9% for Rhodotorula spp., respectively. In 4 of the 141 clinical samples, the BCID-FP panel correctly identified an additional Candida species, undetected by standard-of-care methods. The BCID-FP panel offers a faster turnaround time for identification of fungal pathogens in positive blood cultures that may allow for earlier antifungal interventions and includes C. auris, a highly multidrug-resistant fungus.


Clinical classification of clival chordomas for transnasal approaches.
Endoscopic endonasal approaches (EEAs) are ideal for most chordomas, but there is little information regarding the practical clinical classification of clival chordomas to guide surgery with EEAs. This article investigates a relatively concise and practical clinical classification system for clival chordomas and summarizes the clinical characteristics and operative key points of different clinical types. Here, 55 patients with clival chordomas treated through EEAs from 2012 to 2017 were retrospectively reviewed. Depending on the origin of the notochord and the growth pattern of the tumor, with our introduced Wang's line, these cases of clival chordoma were divided into types I-IV. There were 14 cases of type I-A, 7 cases of type I-B, 10 cases of type II, 10 cases of type III-A, 7 cases of type III-B, and 7 cases of type IV. The gross total resection (GTR) rate of primary and recurrent type I tumors was 64% and 25%, and residual tumors were found mainly in cases with involvement of the cavernous sinus or the posterior upper part of the dorsum sella. The GTR rate of primary and recurrent type II tumors was 85% and 66.6%, respectively. Residual tumors were found in cases with involvement of the petrous apex. The GTR rate of primary and recurrent type III tumors was 75% and 20%, and residual tumors were found in cases with involvement of the parapharyngeal space and dorsal side of C1-2. Residual type I-B and type III-B tumors were found when there was BA or VA adhesion or brain stem invasion. Our new classification method proposed here can be used to guide the resection of clival chordomas through EEAs.


Analysis of the structural requirements for lysosomal membrane targeting using transferrin receptor chimeras.
The sorting of membrane proteins to the lysosome requires tyrosine- or dileucine-based targeting signals. Recycling receptors have similar signals, yet these proteins seldom enter the latter stages of the endocytic pathway. To determine how lysosomal and internalization signals differ, we prepared chimeric molecules consisting of the cytoplasmic tails of CD3 gamma-chain, lysosomal acid phosphatase, and lysosomal-associated membrane glycoprotein-1, each fused to the transmembrane and extracellular domains of the transferrin receptor (TR). Each chimera was expressed on the cell surface and rapidly internalized. Metabolic pulse-chase experiments showed that the CD3 gamma-chain and lysosomal acid phosphatase chimeras, unlike the lysosomal-associated membrane glycoprotein chimera, were rapidly degraded in a post-Golgi compartment following normal glycosylation. Transplantation of signals from CD3 gamma-chain and lysosomal acid phosphatase into the TR cytoplasmic tail in place of the native signal, Y20TRF23, indicated that each signal was sufficient to promote endocytosis but not lysosomal targeting of the resulting mutant. Transplantation of two CD3 signals at specific sites in the TR cytoplasmic tail or a single tyrosine-based signal in a truncated TR tail, however, was sufficient to promote lysosomal targeting. Our results therefore suggest that the relative position of the signal within the cytoplasmic tail is a critical feature that distinguishes lysosomal targeting signals from internalization signals.


Statistically sound calibration curves for chromatographic methods involving negative response data.
A statistical procedure is presented for calibrating chromatographic methods that generate negative chromatographic peaks. The technique is illustrated via data collected during the ion-chromatographic analysis of the ammonium ion in methansulfonic-acid solutions. A peak-integration protocol is explained and subsequent regression data are presented. For the concentration range of 1 to 5 ppb, a quadratic model could be fitted to the calibration data, using ordinary least squares as the fitting technique. The precision was approximately ± 0.5 ppb, at 95% confidence.


Right Ventricle and Epigenetics: A Systematic Review.
There is an increasing recognition of the crucial role of the right ventricle (RV) in determining the functional status and prognosis in multiple conditions. In the past decade, the epigenetic regulation (DNA methylation, histone modification, and non-coding RNAs) of gene expression has been raised as a critical determinant of RV development, RV physiological function, and RV pathological dysfunction. We thus aimed to perform an up-to-date review of the literature, gathering knowledge on the epigenetic modifications associated with RV function/dysfunction. Therefore, we conducted a systematic review of studies assessing the contribution of epigenetic modifications to RV development and/or the progression of RV dysfunction regardless of the causal pathology. English literature published on PubMed, between the inception of the study and 1 January 2023, was evaluated. Two authors independently evaluated whether studies met eligibility criteria before study results were extracted. Amongst the 817 studies screened, 109 studies were included in this review, including 69 that used human samples (e.g., RV myocardium, blood). While 37 proposed an epigenetic-based therapeutic intervention to improve RV function, none involved a clinical trial and 70 are descriptive. Surprisingly, we observed a substantial discrepancy between studies investigating the expression (up or down) and/or the contribution of the same epigenetic modifications on RV function or development. This exhaustive review of the literature summarizes the relevant epigenetic studies focusing on RV in human or preclinical setting.


Ataxia-telangiectasia mutated (ATM) deficiency decreases reprogramming efficiency and leads to genomic instability in iPS cells.
During cell division, one of the major features of somatic cell reprogramming by defined factors, cells are potentially exposed to DNA damage. Inactivation of the tumor suppressor gene p53 raised reprogramming efficiency but resulted in an increased number of abnormal chromosomes in established iPS cells. Ataxia-telangiectasia mutated (ATM), which is critical in the cellular response to DNA double-strand breaks, may also play an important role during reprogramming. To clarify the function of ATM in somatic cell reprogramming, we investigated reprogramming in ATM-deficient (ATM-KO) tail-tip fibroblasts (TTFs). Although reprogramming efficiency was greatly reduced in ATM-KO TTFs, ATM-KO iPS cells were successfully generated and showed the same proliferation activity as WT iPS cells. ATM-KO iPS cells had a gene expression profile similar to ES cells and WT iPS cells, and had the capacity to differentiate into all three germ layers. On the other hand, ATM-KO iPS cells accumulated abnormal genome structures upon continuous passages. Even with the abnormal karyotype, ATM-KO iPS cells retained pluripotent cell characteristics for at least 20 passages. These data indicate that ATM does participate in the reprogramming process, although its role is not essential.


The discrimination of interaural level difference sensitivity functions: development of a taxonomic data template for modelling.
A major cue for the position of a high-frequency sound source in azimuth is the difference in sound pressure levels in the two ears, Interaural Level Differences (ILDs), as a sound is presented from different positions around the head. This study aims to use data classification techniques to build a descriptive model of electro-physiologically determined neuronal sensitivity functions for ILDs. The ILDs were recorded from neurons in the central nucleus of the Inferior Colliculus (ICc), an obligatory midbrain auditory relay nucleus. The majority of ICc neurons (~ 85%) show sensitivity to ILDs but with a variety of different forms that are often difficult to unambiguously separate into different information-bearing types. Thus, this division is often based on laboratory-specific and relatively subjective criteria. Given the subjectivity and non-uniformity of ILD classification methods in use, we examined if objective data classification techniques for this purpose. Our key objectives were to determine if we could find an analytical method (A) to validate the presence of four typical ILD sensitivity functions as is commonly assumed in the field, and (B) whether this method produced classifications that mapped on to the physiologically observed results. The three-step data classification procedure forms the basic methodology of this manuscript. In this three-step procedure, several data normalization techniques were first tested to select a suitable normalization technique to our data. This was then followed by PCA to reduce data dimensionality without losing the core characteristics of the data. Finally Cluster Analysis technique was applied to determine the number of clustered data with the aid of the CCC and Inconsistency Coefficient values. The outcome of a three-step analytical data classification process was the identification of seven distinctive forms of ILD functions. These seven ILD function classes were found to map to the four "known" ideal ILD sensitivity function types, namely: Sigmoidal-EI, Sigmoidal-IE, Peaked, and Insensitive, ILD functions, and variations within these classes. This indicates that these seven templates can be utilized in future modelling studies. We developed a taxonomy of ILD sensitivity functions using a methodological data classification approach. The number and types of generic ILD function patterns found with this method mapped well on to our electrophysiologically determined ILD sensitivity functions. While a larger data set of the latter functions may bring a more robust outcome, this good mapping is encouraging in providing a principled method for classifying such data sets, and could be well extended to other such neuronal sensitivity functions, such as contrast tuning in vision.


Is retrograde intrarenal surgery for the treatment of renal stones with diameters exceeding 2 cm still a hazard?
Major kidney stones have traditionally been treated with percutaneous nephrolithotomy. However, retrograde intrarenal surgery (RIRS), which until a few years ago was considered inappropriate for this purpose, is becoming a viable, attractive alternative. The aim of the current study was to assess the efficacy and safety of RIRS combined with holmium laser lithotripsy for the treatment of stones > 2 cm in diameter in a large series of patients, reporting complications according to the Clavien-Dindo classification. By retrospective analysis, we identified a total of 162 patients who were affected by stones greater than 2 cm in diameter and who had undergone RIRS. We reviewed demographic and stone characteristics, intraoperative and postoperative outcomes, and complications. The mean stone size was 2.7 cm +/- 0.6 cm. The primary, secondary, and tertiary stone-free rates were 66%, 80.9%, and 87.7%, respectively. The mean number of procedures per patient was 1.48. The complication rates according to the Clavien-Dindo classification were Clavien I in 20.4% of patients, Clavien II in 0%, Clavien III in 4.9%, Clavien IV in 0.6%, and Clavien V in 0%. As an alternative to standard procedures for the treatment of renal calculi greater than 2 cm in diameter, RIRS is safe and effective, with a low complication rate.


App-Delivered Cognitive-Behavioral Therapy for Insomnia Among Patients with Comorbid Musculoskeletal Complaints and Insomnia Referred to 4-Week Inpatient Multimodal Rehabilitation: Protocol for a Randomized Clinical Trial.
Insomnia is prevalent among patients receiving treatment for long-term musculoskeletal complaints in inpatient rehabilitation settings. Cognitive-behavioral therapy for insomnia (CBT-I) is effective for improving sleep quality in patients with pain, but a lack of therapists often limits the capacity to use this therapy in rehabilitation programs. The aim of this randomized clinical trial (RCT) is to evaluate the effectiveness of app-delivered CBT-I adjunct to inpatient multimodal rehabilitation for individuals with comorbid musculoskeletal complaints and insomnia, compared with rehabilitation (usual care) only. This RCT has two parallel arms: 1) inpatient multimodal rehabilitation and 2) app-delivered CBT-I adjunct to inpatient multimodal rehabilitation. Patients referred to Unicare Helsefort (Norway) with long-term chronic musculoskeletal complaints are invited to the study. Eligible and consenting participants will be randomized to the intervention and usual care at a ratio of 2:1. Assessments will be carried out at baseline (prior to randomization), 6 weeks (at the end of rehabilitation), 3 months (primary outcome), as well as 6 and 12 months after the rehabilitation. The primary outcome is insomnia severity measured at 3 months. Secondary outcomes include pain intensity, health-related quality of life, fatigue, physical function, work ability, expectations about sick leave length, sick leave, and prescribed medication. Exploratory analyses are planned to identify moderators and mediators of the effect of the app-delivered intervention. This RCT will provide novel knowledge about the effectiveness of app-delivered CBT-I as an adjunct to usual care among patients participating in inpatient multimodal pain rehabilitation. Regardless of the results from this trial, the results will improve our understanding of the utility of dCBT-I in the field of rehabilitation and the importance of adding sleep therapy to this patient group. This trial was prospectively registered in ClinicalTrials.gov October 10, 2022 (ClinicalTrials.gov identifier: NCT05572697).


Full-spectrum CT reconstruction using a weighted least squares algorithm with an energy-axis penalty.
Recent developments in X-ray detectors have created the potential to perform energy-sensitive X-ray computed tomography (CT); that is, to reconstruct a series of CT images associated with different X-ray energies from a single scan. In this paper we propose a penalized weighted least squares (PWLS) algorithm for reconstruction of polychromatic energy-differentiated X-ray CT data and a unique experimental setup to take energy-differentiated X-ray CT data. The experimental setup is designed to acquire a complete X-ray spectrum for every projection ray. We use these data to estimate the linear attenuation coefficient as a function of energy for every pixel in the reconstructed attenuation map. We use prior knowledge of the properties of attenuation spectra to smooth the reconstructions, significantly reducing the noise and improving the contrast-to-noise ratio (CNR) in the reconstructed images without significantly biasing the data. We conclude that this algorithm is an effective method for reconstructing energy-sensitive CT data and provides justification for further research in energy sensitive CT systems.


Moving towards the detection of frailty with biomarkers: A population health study.
Aging adults experience increased health vulnerability and compromised abilities to cope with stressors, which are the clinical manifestations of frailty. Frailty is complex, and efforts to identify biomarkers to detect frailty and pre-frailty in the clinical setting are rarely reproduced across cohorts. We developed a predictive model incorporating biological and clinical frailty measures to identify robust biomarkers across data sets. Data were from two large cohorts of older adults: "Invecchiare in Chianti (Aging in Chianti, InCHIANTI Study") (n = 1453) from two small towns in Tuscany, Italy, and replicated in the Atherosclerosis Risk in Communities Study (ARIC) (n = 6508) from four U.S. communities. A complex systems approach to biomarker selection with a tree-boosting machine learning (ML) technique for supervised learning analysis was used to examine biomarker population differences across both datasets. Our approach compared predictors with robust, pre-frail, and frail participants and examined the ability to detect frailty status by race. Unique biomarker features identified in the InCHIANTI study allowed us to predict frailty with a model accuracy of 0.72 (95% confidence interval (CI) 0.66-0.80). Replication models in ARIC maintained a model accuracy of 0.64 (95% CI 0.66-0.72). Frail and pre-frail Black participant models maintained a lower model accuracy. The predictive panel of biomarkers identified in this study may improve the ability to detect frailty as a complex aging syndrome in the clinical setting. We propose several concrete next steps to keep research moving toward detecting frailty with biomarker-based detection methods.


Simvastatin inhibits the division and induces neurite-like outgrowth in PC12 cells.
Simvastatin, a potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. inhibited cell division in a dose dependent fashion and induced neurite-like outgrowth in PC12 cells. The neurite-like outgrowth was detectable at 0.5 microg/ml of simvastatin 24 h after the treatment. The responses to simvastatin were completely prevented by incubating the cells with mevalonate. In contrast to simvastatin, pravastatin, a similar HMG-CoA reductase inhibitor but lipophobic, had no effect on the cells. The results provide new possibilities for the central nervous system (CNS) side effects of simvastatin therapy.


Development of a suspension microarray for the genotyping of African swine fever virus targeting the SNPs in the C-terminal end of the p72 gene region of the genome.
African swine fever virus (ASFV) causes one of the most dreaded transboundary animal diseases (TADs) in Suidae. African swine fever (ASF) often causes high rates of morbidity and mortality, which can reach 100% in domestic swine. To date, serological diagnosis has the drawback of not being able to differentiate variants of this virus. Previous studies have identified the 22 genotypes based on sequence variation in the C-terminal region of the p72 gene, which has become the standard for categorizing ASFVs. This article describes a genotyping assay developed using a segment of PCR-amplified genomic DNA of approximately 450 bp, which encompasses the C-terminal end of the p72 gene. Complementary paired DNA probes of 15 or 17 bp in length, which are identical except for a single nucleotide polymorphism (SNP) in the central position, were designed to either individually or in combination differentiate between the 22 genotypes. The assay was developed using xMAP technology; probes were covalently linked to microspheres, hybridized to PCR product, labelled with a reporter and read in the Luminex 200 analyzer. Characterization of the sample was performed by comparing fluorescence of the paired SNP probes, that is, the probe with higher fluorescence in a complementary pair identified the SNP that a particular sample possessed. In the final assay, a total of 52 probes were employed, 24 SNP pairs and 4 for general detection. One or more samples from each of the 22 genotypes were tested. The assay was able to detect and distinguish all 22 genotypes. This novel assay provides a powerful novel tool for the simultaneous rapid diagnosis and genotypic differentiation of ASF.


Brown-colored semen in men with spinal cord injury.
The interesting condition of brown-colored semen has often been observed during assisted ejaculation of men with spinal cord injury (SCI). This condition has not been reported in the literature, and its cause is unknown. To investigate this condition, the present study examined the incidence and quality of brown semen and its relationship to level of SCI, time since SCI, number of successive ejaculations, ejaculation frequency, and ejaculation method in a total of 664 semen specimens from 162 SCI men. In addition, a microscopic evaluation was performed on brown semen specimens from SCI men, not-brown specimens from SCI men, and normally colored specimens from normal men. The results showed that 27% of SCI subjects had brown semen on at least one ejaculation. There was no difference between men producing and men not producing brown semen in age, level of injury, or years postinjury. The duration of an ejaculation, number of successive ejaculations, and frequency of ejaculation were not associated with occurrence of brown semen. Sperm concentration and sperm motility were not significantly different in brown and not-brown specimens. Specimens from subjects who produced brown semen had similar pH but lower volume than specimens from subjects who did not produce brown semen. Brown semen had a thin consistency more often than not-brown semen. Brown specimens contained intact red blood cells (RBCs) and/or heme pigment more often than not-brown specimens; however, one half and one third of the specimens, respectively, contained neither RBCs nor heme pigment. The cause of brown semen is unknown but may relate to seminal-vesicle dysfunction.


Commitment to natural killer cells requires the helix-loop-helix inhibitor Id2.
We have previously described how T and natural killer (NK) lineage commitment proceeds from common T/NK progenitors (p-T/NK) in the murine fetal thymus (FT), with the use of a clonal assay system capable of discriminating p-T/NK from unipotent T or NK lineage-committed progenitors (p-T and p-NK, respectively). The molecular mechanisms controlling the commitment processes, however, are yet to be defined. In this study, we investigated the progenitor activity of FT cells from Id2-/- mice that exhibit defective NK cell development. In the Id2-/- FT, NK cells were greatly reduced, and a cell population that exclusively contains p-NK in the wild-type thymus was completely missing. Id2-/- FT progenitors were unable to differentiate into NK cells in IL-2-supplemented-FT organ culture. Single progenitor analysis demonstrated that all Id2-/- fetal thymic progenitors are destined for the T cell lineage, whereas progenitors for T/NK, T, and NK cell lineages were found in the control. Interestingly, the total progenitor number was similar between Id2-/- and Id2+/+ embryos analyzed. Expression of Id2 was correlated with p-NK activity. Our results suggest that Id2 is indispensable in thymic NK cell development, where it most probably restricts bipotent T/NK progenitors to the NK cell lineage.


Ribavirin reduces clinical signs and pathological changes of experimental autoimmune encephalomyelitis in Dark Agouti rats.
The effect of ribavirin on development of experimental autoimmune encephalomyelitis (EAE) was investigated. The disease was induced in genetically susceptible Dark Agouti rats with syngeneic spinal cord homogenate in complete Freund's adjuvant (SCH-CFA). Depending on the amount of mycobacteria in CFA, the animals developed either moderate or severe EAE. Ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) was applied i.p. at a daily dosage of 30 mg/kg in two treatment protocols: from the start of immunization (preventive treatment) or from the onset of the first EAE signs after the induction (therapeutic treatment). Signs of EAE began between 7 and 9 days after induction and peaked at days 11-13. In moderate EAE (mean maximal severity score 3.33 +/- 0.21), the recovery was completed by days 23-26, whereas, in severe EAE (mean maximal severity score 4.5 +/- 0.23), obvious recovery was not detected. Preventive ribavirin treatment significantly decreased clinical signs after both moderate (score 1.75 +/- 0.25, P < 0.05) and severe (score 3.62 +/- 0.31, P < 0.015) immunization. Also, disease manifestations were reduced by therapeutic treatment of ribavirin (mean maximal severity score 2.5 +/- 0.2 vs. 3.33 +/- 0.21 in controls, P < 0.005) but less so in comparison with preventive treatment. Analysis of the effects of ribavirin on histopathologic changes in the spinal cord tissue revealed a reduction of mononuclear cell infiltrates, composed of T cells and macrophages/microglia, and the absence of demyelination, which were pronounced in control EAE animals. Beneficial effects of preventive and therapeutic treatment with ribavirin on development of EAE suggest this nucleoside analogue as a useful candidate for therapy in multiple sclerosis.


Evidence of a high frequency of HIV-1 subtype F infections in a heterosexual population in Buenos Aires, Argentina.
We analyzed HIV-1 genetic variability, phylogenetic relationships, and association with transmission modes among 58 HIV-1-infected patients from Buenos Aires City, Argentina. The 58 strains were classified as env(gp41) HIV-1 group M subtype B (n = 34) and subgroup F1 of subtype F (n = 24). Potential recombinants combining parts of viral regions from different subtypes, B(prot)/F(env) and F(prot)/B(env), were found in two patients, and a dual infection with HIV-1 prot subtypes B and F was identified in one individual. Epidemiologic analysis of behavioral risks revealed that the frequency of infection with subtype F viruses was significantly higher (p < 0.0001) among heterosexual patients (71%) compared with homosexual patients (11%). The spread of non-B subtypes into heterosexual populations may be more common than previously thought. Our findings provide important information for monitoring the transmission of HIV-1 strains among different risk groups in Argentina as well as for vaccine development.


Water intake disorder in a DEND syndrome afflicted patient with R50P mutation.
In this study, we present a case of developmental delay, epilepsy and neonatal diabetes (DEND) syndrome in a young male patient with the R50P mutation located in the Kir6.2 subunit of the ATP-sensitive K(+) (KATP) channel. Whereas most patients with DEND syndrome are resistant to sulfonylurea therapy, our patient was responsive to sulfonylurea, lacked the most common neurological symptoms, such as epilepsy, but refused to drink water. His serum electrolytes and plasma osmolarity were normal but the serum vasopressin level was increased. To investigate the underlying mechanism of his water intake disorder, a 5 μL aliquot of 340 μM KATP channel opener diazoxide or 100 μM KATP channel inhibitor glibenclamide was injected into the third ventricle of the rat brain, and water intake was monitored. Although the injection of glibenclamide had no effect, injection of diazoxide significantly increased water intake by about 1.5 fold without affecting food intake. This result indicates that the KATP channel activity in the brain may have an influence on water intake. Here, we present the first case of a DEND syndrome-afflicted patient with water intake disorder and increased serum vasopressin level, possibly related to altered KATP channel activity.


Epithelial anion transporter pendrin contributes to inflammatory lung pathology in mouse models of Bordetella pertussis infection.
Pertussis disease, characterized by severe and prolonged coughing episodes, can progress to a critical stage with pulmonary inflammation and death in young infants. However, there are currently no effective treatments for pertussis. We previously studied the role of pertussis toxin (PT), an important Bordetella pertussis virulence factor, in lung transcriptional responses to B. pertussis infection in mouse models. One of the genes most highly upregulated in a PT-dependent manner encodes an epithelial transporter of bicarbonate, chloride, and thiocyanate, named pendrin, that contributes to asthma pathology. In this study, we found that pendrin expression is upregulated at both gene and protein levels in the lungs of B. pertussis-infected mice. Pendrin upregulation is associated with PT production by the bacteria and with interleukin-17A (IL-17A) production by the host. B. pertussis-infected pendrin knockout (KO) mice had higher lung bacterial loads than infected pendrin-expressing mice but had significantly reduced levels of lung inflammatory pathology. However, reduced pathology did not correlate with reduced inflammatory cytokine expression. Infected pendrin KO mice had higher levels of inflammatory cytokines and chemokines than infected pendrin-expressing mice, suggesting that these inflammatory mediators are less active in the airways in the absence of pendrin. In addition, treatment of B. pertussis-infected mice with the carbonic anhydrase inhibitor acetazolamide reduced lung inflammatory pathology without affecting pendrin synthesis or bacterial loads. Together these data suggest that PT contributes to pertussis pathology through the upregulation of pendrin, which promotes conditions favoring inflammatory pathology. Therefore, pendrin may represent a novel therapeutic target for treatment of pertussis disease.


Synchronized oscillations, traveling waves, and jammed clusters induced by steric interactions in active filament arrays.
Autonomous active, elastic filaments that interact with each other to achieve cooperation and synchrony underlie many critical functions in biology. The mechanisms underlying this collective response and the essential ingredients for stable synchronization remain a mystery. Inspired by how these biological entities integrate elasticity with molecular motor activity to generate sustained oscillations, a number of synthetic active filament systems have been developed that mimic oscillations of these biological active filaments. Here, we describe the collective dynamics and stable spatiotemporal patterns that emerge in such biomimetic multi-filament arrays, under conditions where steric interactions may impact or dominate the collective dynamics. To focus on the role of steric interactions, we study the system using Brownian dynamics, without considering long-ranged hydrodynamic interactions. The simulations treat each filament as a connected chain of self-propelling colloids. We demonstrate that short-range steric inter-filament interactions and filament roughness are sufficient - even in the absence of inter-filament hydrodynamic interactions - to generate a rich variety of collective spatiotemporal oscillatory, traveling and static patterns. We first analyze the collective dynamics of two- and three-filament clusters and identify parameter ranges in which steric interactions lead to synchronized oscillations and strongly occluded states. Generalizing these results to large one-dimensional arrays, we find rich emergent behaviors, including traveling metachronal waves, and modulated wavetrains that are controlled by the interplay between the array geometry, filament activity, and filament elasticity. Interestingly, the existence of metachronal waves is non-monotonic with respect to the inter-filament spacing. We also find that the degree of filament roughness significantly affects the dynamics - specifically, filament roughness generates a locking-mechanism that transforms traveling wave patterns into statically stuck and jammed configurations. Taken together, simulations suggest that short-ranged steric inter-filament interactions could combine with complementary hydrodynamic interactions to control the development and regulation of oscillatory collective patterns. Furthermore, roughness and steric interactions may be critical to the development of jammed spatially periodic states; a spatiotemporal feature not observed in purely hydrodynamically interacting systems.


Cultivation and maintenance of Sphaerophorus necrophorus. I. An anaerobic medium for aerobic incubation.
Out of 185 media formulated and studied for the growth of Sphaerophorus necrophorus, ten were selected for intensive investigation. Their ability to promote growth was compared photometrically. Medium 156 made up of Brewer's thioglycollate broth, yeast extract, L-cystine, and ascorbic acid, was found to yield a very heavy growth. The viability of S. necrophorus was maintained indefinitely by weekly subcultures. When not subcultured, all isolates remained viable for fifteen weeks and some isolates for 30 weeks at 37 degrees C.Twenty-nine isolates were tested. No variation in maximum growth was noticed. Medium 156 is an optimum medium for S. necrophorus. It can be incubated aerobically without interfering with maximum growth. The medium does not deteriorate when stored for at least 12 weeks at room temperature.


[Severe HELLP syndrome with temporary kidney and lung failure].
This report is on a severe case fo a HELLP-syndrome (H haemolysis, EL elevated liver enzymes, and LP low platelets). A 32-year old gravida developed severe preeclampsia with epigastric pain at 33 weeks' gestation. During a few hours post partum she showed disseminated intravascular coagulation (DIC) and required intensive care. The severe HELLP-syndrome was combined with a fast increasing acute respiratory distress syndrome (ARDS) and acute oligo-anuric renal failure. She was treated in the intensive-care unit for several days with artificial respiration, 10 acute haemodialyses, 4 plasma exchanges with fresh-frozen plasma and many blood and platelet transfusions. An early Caesarean section and treatment in the intensive care unit managed to turn the otherwise complicated progression of the disease. It is pointed out that plasma exchange with fresh-frozen plasma is a rarely employed treatment.


Criminal behavior in opioid-dependent patients before and during maintenance therapy: 6-year follow-up of a nationally representative cohort sample.
Lifetime prevalence of opioid dependence is about 0.4% in western countries. Opioid-dependent patients have high morbidity and mortality and a high risk of criminal behavior. Few studies have addressed the long-term impact of opioid maintenance therapy on convictions and criminal behavior. The PREMOS study is a prospective, longitudinal, naturalistic clinical study of a nationally representative sample of 2694 opioid-dependent patients to investigate convictions and criminal behavior at baseline and after 6 years of maintenance treatment. At follow-up, 2284 patients still were eligible (84.7%). A comprehensive assessment including a patient and doctor questionnaire, and the EuropASI was completed at baseline and follow-up. Data on criminality at follow-up had been received for 1147 (70.6%) patients. A large number (84.5%) of them had been charged or convicted at any time before baseline assessment, most frequently with drug-related offenses (66.8%), acquisitive crime (49.1%), or acts of violence (22.0%). Reported charges and convictions had declined to 17.9% for the last 12 months before follow-up, which was also reflected by a significant decrease in the EuropASI subscore "legal problems" from 1.52 at baseline to 0.98 after 6 years. These data indicate a significant and clinically relevant reduction in criminal behavior in opioid-dependent patients in long-term maintenance treatment. Maintenance therapy is effective in the reduction in both narcotics-related and acquisition crime.


Mitochondrial gene-knockout (rho0) cells: a versatile model for exploring the secrets of trans-plasma membrane electron transport.
Plasma membrane electron transport (tPMET) pathways have been identified in all living cells, and a wide variety of tools have been used to study these processes. In our laboratory we have used the cell-impermeable tetrazolium dye WST-1, together with the mitochondrial gene knockout (rho0) cell model, to investigate one of these pathways. We have shown that growth of HL60rho0 cells is dependent on oxygen, and that these cells consume oxygen at the cell surface. Similarities in inhibition profiles between non-mitochondrial oxygen consumption and WST-1 reduction suggest that both systems share a common tPMET pathway. In support of this, oxygen was shown to compete with the intermediate electron acceptor that mediates WST-1 reduction, for reducing electrons. The observation that tPMET activity is higher in rho0 cells compared to their mitochondrially-competent counterparts was shown to be the result of competition between the mitochondrial and plasma membrane electron transport systems for intracellular reducing equivalents. Elevated rates of dye reduction appear to be mediated through increased expression of the key components of tPMET, which include the cell surface NADH oxidase, CNOX. These findings have played a critical role in shaping our current understanding of the mechanisms of this particular pathway of tPMET.


Learning from the Experience of the COVID-19 Pandemic: A New Paradigm for Occupational Biohazard Assessment and Management.
The COVID-19 pandemic has affected workplaces in many different aspects. In this scenario, Occupational Physicians played a crucial role in assessing and managing the risk of SARS-CoV-2 infection and associated diseases to guarantee workers' health and the safety of workplaces. However, the pandemic experience has drawn attention to several critical issues in overall biohazard prevention and management strategies, originating from important knowledge gaps in our scientific understanding. An extensive analysis of the relevant hurdles that have emerged in our medical field can bring valuable lessons for the post pandemic future, not only in preparation for possible new pathogens with pandemic potential but also with principles and concepts applicable to managing all biological agents. In particular, a paradigm shift is needed to properly approach occupational diseases caused by infective agents, accurately define the "case", assess exposure and possible causal relationship with work appropriately, and effectively manage the specific risk through implementing appropriate preventive and protective measures. In this framework, the Occupational Physician should expand his contribution based on his unique expertise and specific competencies, confirming his role as the go-to consultant in all occupational health matters, but also in a multidisciplinary approach, considering different scientific expertise and evidence.


Durian Fruits Discovered as Superior Folate Sources.
Durian (Durio zibethinus) is a tropical fruit grown in Southeast Asia and highly appreciated by consumers throughout Asia. Folates are a group of vitamins and are essential nutrients for humans. Here we present the folate analysis of different durian cultivars as well as diverse durian products. An LC-MS/MS method and the application of a stable isotope dilution assay (SIDA) was used for quantitation of the folate vitamers 5-methyltetrahydrofolate, 5-formyltetrahydrofolate, 10-formylfolate, tetrahydrofolate, and pteroylmonoglutamic acid by using [13C5]-labeled internal standards. Total folates varied from 175 to 440 μg/100 g for durian arils and from 15.0 to 417 μg/100 g for durian products. These contents are extraordinarily high compared to other fruits and may be correlated to the upregulated methionine biosynthesis pathway reported recently. In summary, the tropical fruit durian can be considered as a very rich dietary source of natural folates.


Mean lifetime survival estimates following solid organ transplantation in the US and UK.
Accurately estimating mean survival after solid organ transplant (SOT) is crucial for efficient healthcare resource allocation decisions. However, registry-based post-transplant recipient survival estimates vary greatly and are incomplete. Often, the methods used in lifetime survival extrapolation may not fit complex transplant data and therefore alternative methods are required. We aimed to explore the flexible cubic spline methodology as a meaningful alternative for estimating lifetime survival following SOT. Survival analyses were conducted in kidney, liver, heart, and lung transplant recipients. Mean survival was estimated using flexible cubic splines on the hazard scale fitted with three knots, based on where hazards changed direction, clinical advice, and best-fit curve using Akaike and Bayesian information criterion. The tail was extrapolated when data were no longer available. Extrapolation tails were compared with general population mortality, using age-matched life table hazards, and the highest hazards were taken at all times. We found that mean survival post-transplant was longest for kidney transplants (US: 22.79 years; UK: 26.58 years), followed by liver (US: 20.90 years; UK: 20.38 years), heart (US: 14.82 years; UK: 15.85 years), and lung (US: 9.28 years; UK: 9.21 years). A sensitivity analysis using two knots found differences in survival ranging from -1.30 to +4.83 years across SOTs examined. This study does not represent individual patient survival, survival by age groups, multiple-organ transplants, or assess factors that may impact overall or organ survival. Our study estimates reflect real-world survival following SOTs and demonstrate the importance of including long-term hazards in survival estimations. These lifetime survival estimates can be used by decision-makers in situations where means are preferred over medians (e.g. population projections, budgetary estimates, and cost-effectiveness models) and can thus offer a meaningful alternative to the estimates used and accepted in current practice.


The new simplified Sim-Gordon orthodontic analysis.
The new Sim-Gordon Computerized Analysis is simple to use, basic in the orthodontic diagnostic values that need to be measured and entered, and serves as an extremely useful guide for the treatment planning of orthodontic patients. It will run on any IBM compatible computer, and uses less than 740 Kb of space on a disk. So far as is known, all insurance companies will accept it. It is a pleasure to announce the availability of this reasonable and cost-effective, simplified, IAO-accepted, professional orthodontic diagnostic system to our fellow practitioners. The authors would like to thank Dr. Duane Keller, Dr. Yosh Jefferson, Dr. Thomas Hughes, Dr. Rudy Postema, Dr. Michel Champagne, Dr. John Byland, Dr. Kenneth Lyle, and Dr. Janet Doerr for their helpful suggestions and aid in the selection of values to be measured.


Factors Affecting Length of Stay and Complications After Elective Anterior Cervical Discectomy and Fusion: A Study of 2164 Patients From The American College of Surgeons National Surgical Quality Improvement Project Database (ACS NSQIP).
Retrospective review of the prospective American College of Surgeons National Surgical Quality Improvement Project (ACS NSQIP) database with 30-day follow-up of 2164 patients undergoing elective anterior cervical discectomy and fusion (ACDF). To determine factors independently associated with increased length of stay (LOS) and complications after ACDF to facilitate preoperative planning and setting of realistic expectations for patients and providers. The effect of individual preoperative factors on LOS and complications has been evaluated in small-scale studies. Large database analysis with multivariate analysis of these variables has not been reported. The ACS NSQIP database from 2005 to 2010 was queried for patients undergoing ACDF procedures. Preoperative and perioperative variables were collected. Multivariate regression determined significant predictors (P<0.05) of extended LOS and complications. Average LOS was 2.0±4.0 days (mean±SD) with a range of 0-103 days. By multivariate analysis, age 65 years and above, functional status, transfer from facility, preoperative anemia, and diabetes were the preoperative factors predictive of extended LOS. Major complications, minor complications, and extended surgery time were the perioperative factors associated with increased LOS. The elongating effect of these variables was determined, and ranged from 0.5 to 5.0 days. Seventy-one patients (3.3%) had a total of 92 major complications, including return to operating room (40), venous thrombotic events (13), respiratory (21), cardiac (6), mortality (5), sepsis (4), and organ space infection (3). Multivariate analysis determined ASA score ≥3, preoperative anemia, age 65 years and above, extended surgery time, and male sex to be predictive of major complications (odds ratios ranging between 1.756 and 2.609). No association was found between levels fused and LOS or complications. Extended LOS after ACDF is associated with factors including age, anemia, and diabetes, as well as the development of postoperative complications. One in 33 patients develops a major complication postoperatively, which are associated with an increased LOS of 5 days.


[Systems biology and personalized medicine: to be or not to be?].
The review is devoted to the widely discussed problems of the feasibility of "systems biology" and "P4-personalized (systems) medicine" from the standpoint of complex living systems. The following conclusions are made. 1. It is impossible to reach the ultimate goals of systems biology and medicine based solely on data of genomics and other 'omics'. Systems biology may be efficient for an approximate description of certain functional modules provided that there are experimental data for the majority of the components of the system under study. 2. P4-personalized (systems) medicine based on systems biology is unrealistic fundamentally and technically, as well as from the economic point of view. 3. A possible way is to search for the targets common for all or for large groups of individuals, and the development of postgenomic generalized medicine. 4. Also realistic are some of currently developing options of personalized medicine, such as e. g. the use of patient stem cells that are returned to the patient after culturing, or of gene-modified infiltrating T-lymphocytes in so-called chimeric antigen receptor (CAR) cancer therapy. CAR therapy is a personalized treatment that uses T-lymphocytes taken from a patient and gene-modified in such a way that to recognize and kill cancer cells. 5. Despite of numerous claims, the paradigms of the postgenomic sciences were not changed. Traditional approaches of molecular biology, genetics, biochemistry, and physiology still remain in force in the postgenomic era. They are enforced due to the data obtained by 'omics'. These data may be a base for putting forward and testing hypotheses about the mechanisms of functional processes.


[Purification and certain properties of pyruvate decarboxylase from bovine brain].
A procedure of isolation and purification of pyruvate decarboxylase (PDC) from bovine brain is worked out. 350-fold purified enzyme preparation was homogenous under polyacrylamide gel electrophoresis. Molecular weight of PDC from bovine brain was estimated to be 180 000 by means of gel chromatography through Sephadex G-200. The protein was eluted in two peaks (with molecular weight of 180 000 and 90 000 respectively). After the treatment of the enzyme preparation with 6 M guanidine chloride. Probably, partial dissociation of the enzyme molecule into two subunits takes place in this case. Data on paper chromatography confirmed that highly purified PDC preparations from bovine brain were isolated as apoenzyme, since they were almost free of TPP.


Balance of Macrophage Activation by a Complex Coacervate-Based Adhesive Drug Carrier Facilitates Diabetic Wound Healing.
Uncontrolled and sustained inflammation disrupts the wound-healing process and produces excessive reactive oxygen species, resulting in chronic or impaired wound closure. Natural antioxidants such as plant-based extracts and natural polysaccharides have a long history in wound care. However, they are hard to apply to wound beds due to high levels of exudate or anatomical sites to which securing a dressing is difficult. Therefore, we developed a complex coacervate-based drug carrier with underwater adhesive properties that circumvents these challenges by enabling wet adhesion and controlling inflammatory responses. This resulted in significantly accelerated wound healing through balancing the pro- and anti-inflammatory responses in macrophages. In brief, we designed a complex coacervate-based drug carrier (ADC) comprising oligochitosan and inositol hexaphosphate to entrap and release antioxidant proanthocyanins (PA) in a sustained way. The results from in vitro experiments demonstrated that ADC is able to reduce LPS-stimulated pro-inflammatory responses in macrophages. The ability of ADC to reduce LPS-stimulated pro-inflammatory responses in macrophages is even more promising when ADC is encapsulated with PA (ADC-PA). Our results indicate that ADC-PA is able to polarize macrophages into an M2 tissue-healing phenotype via up-regulation of anti-inflammatory and resolution of inflammatory responses. Treatment with ADC-PA around the wound beds fine-tunes the balance between the numbers of inducible nitric oxide synthase-positive (iNOS+) and mannose receptor-negative (CD206-) M1 and iNOS-CD206+ M2 macrophages in the wound microenvironment compared to controls. Achieving such a balance between the numbers of iNOS+CD206- M1 and iNOS-CD206+ M2 macrophages in the wound microenvironment has led to significantly improved wound closure in mouse models of diabetes, which exhibit severe impairments in wound healing. Together, our results demonstrate for the first time the use of a complex coacervate-based drug delivery system to promote timely resolution of the inflammatory responses for diabetic wound healing by fine-tuning the functions of macrophages.


Pathology of Naturally Occurring Bacillary Hemoglobinuria in Cattle.
Clostridium haemolyticum causes bacillary hemoglobinuria (BH), an infectious and usually fatal disease that occurs mostly in cattle, which is clinically characterized by jaundice, hemoglobinuria, and anemia. The trematode Fasciola hepatica has been commonly reported as the main predisposing factor that triggers this condition. The authors evaluated 20 naturally occurring cases of bovine BH to characterize the pathology and pathogenesis of the disease. Grossly, the most consistent finding was a large, frequently single focus of necrosis surrounded by a red to purple halo, observed most frequently on the parietal surface of the right and left hepatic lobes. Other findings were jaundice, dark-brown discoloration of kidneys, and red urine in the urinary bladder. Microscopically, characteristic lesions were locally extensive, necrotizing hepatitis with thrombosis and numerous intralesional Gram-positive rod-shaped bacteria, and acute renal tubular necrosis. By immunohistochemistry, many hepatocytes outside the necrotic focus in the liver were positive for activated caspase 3, suggesting that those cells were undergoing apoptosis. Ultrastructural evaluation revealed hepatocyte necrosis, hemolysis, and clumps of vegetative and sporulating bacilli within the liver. Polymerase chain reaction for the C. haemolyticum beta toxin gene was positive in randomly selected liver samples. No gross or microscopic lesions indicative of fascioliasis were detected in the liver of any animal, suggesting that other yet undetermined predisposing factors were associated with these cases of BH.


False rifampicin resistant results using Xpert MTB/RIF on urine samples in hospitalised HIV-infected patients.
A small proportion of false rifampicin resistant results have previously been reported using GeneXpert MTB/RIF version G4 on sputum samples; however, this has not been investigated for urine samples in HIV-associated tuberculosis (TB). We sought to determine the proportion of false rifampicin resistant results using Xpert MTB/RIF version G4 on urine samples among HIV-infected inpatients investigated for TB. Hospitalised HIV-infected patients undergoing systematic TB testing from two cohorts in Cape Town, South Africa, were enrolled. All patients with ≥1 urine Xpert result available were included. Rifampicin resistant urine Xpert results were classified into three mutually exclusive groups: (1) true rifampicin resistance, (2) false rifampicin resistance or (3) unknown after review of available microbiologic and clinical data. Overall, 1171 patients were included, from whom a total of 1704 urine Xpert results were available on unconcentrated and/or concentrated urine samples. There were 416 samples positive for TB (24.4% [95% CI 22.4-26.5]), of which 43/413 (10.4% [95% CI 7.6-13.8]) were rifampicin resistant (after excluding three results that were falsely positive due to contamination). Of 43 rifampicin resistant Xpert results (among 40 patients), 30 were classified as true resistance, 11 as false resistance and 2 could not be classified. Excluding unclassifiable results, 30/41 results were confirmed as true-positive urine Xpert rifampicin resistance (positive predictive value: 73.2% [95% CI 57.1-85.8]). Urine Xpert testing showed a high proportion of false rifampicin resistance results. Urine Xpert rifampicin resistant results should be interpreted cautiously and confirmed when possible.


Lower extremity dexterity is associated with agility in adolescent soccer athletes.
Agility is important for sport performance and potentially injury risk; however, factors affecting this motor skill remain unclear. Here, we evaluated the extent to which lower extremity dexterity (LED) and muscle performance were associated with agility. Fourteen male and 14 female soccer athletes participated. Agility was evaluated using a hopping sequence separately with both limbs and with the dominant limb only. The LED test evaluated the athletes' ability to dynamically regulate foot-ground interactions by compressing a spring prone to buckling with the lower limb. Muscle performance included hip and knee isometric strength and vertical jump height. Correlation analyses were used to assess the associations between muscle performance, LED, and agility. Multiple regression models were used to determine whether linear associations differed between sexes. On average, the female athletes took longer to complete the agility tasks than the male athletes. This difference could not be explained by muscle performance. Conversely, LED was found to be the primary determinant of agility (double limb: R(2) = 0.61, P < 0.001; single limb: R(2) = 0.63, P < 0.001). Our findings suggest that the sensorimotor ability to dynamically regulate foot-ground interactions as assessed by the LED test is predictive of agility in soccer athletes. We propose that LED may have implications for sport performance, injury risk, and rehabilitation.


Optical Real-Time Cardiorenal Toxin Uric Acid Measurement During Hemodialysis Using a Miniaturized Optical Sensor.
Patients with chronic kidney disease (CKD) are at higher cardiovascular risk than the general population. Cardiovascular diseases, vascular calcification among them, are the leading cause of death in these patients. Factors influencing vascular calcification are oxidative stress, inflammation, and accumulation of uremic toxins during CKD. Uric acid is a cardiorenal toxin that accumulates in the case of kidney malfunction. The primary therapy for replacing kidney function and removing toxins from end-stage renal disease patients is hemodialysis. Effective removal of toxins can be estimated by blood or dialysate lab analysis or optical monitoring. In this study, the authors tested a miniaturized optical sensor for monitoring uric acid levels and removal for the first time in a more extensive clinical study, including Hemodialysis (HD) and Post-dilutional online hemodiafiltration (HDF) procedures with different settings in Tallinn, Estonia. The results (Mean±SD, Lab vs. Sensor) of the uric acid concentration 57.20±34.05 vs. 57.22±33.09 µmol/L, reduction ratio 68.72±10.91 vs. 67.89±12.48 %, and total removed amount 7.00±2.10 vs. 7.33±2.29 mmol did not differ significantly from the values obtained from the clinical laboratory (p<0.05).Clinical Relevance-During this study, a miniaturized optical sensor was tested for the first time in the clinic in different dialysis settings. The results confirm that the sensor is reliable for regularly monitoring cardiorenal toxin uric acid removal during hemodialysis.


Lifting the curtain of silence: survivors speak about rape behind bars.
In the struggle to end sexual violence behind bars, personal stories of abuse serve as an important advocacy tool for organizations such as Stop Prisoner Rape (SPR). The first-person accounts of men and women who have endured this abuse help to personalize, and thereby, humanize the issue. Statistics about the frequency of prisoner rape are powerful, but they can also be numbing, conveying the sense that nothing can be done to stop the problem. Personal accounts in contrast, have an emotional impact that encourages action. Speaking out about abuse also helps survivors, freeing them from a sense of shame, guilt, and humiliation and providing an avenue of political engagement that can be tremendously empowering. This article presents the first-persona accounts of four individuals whose lives were powerfully affected by rape behind bars.


A hybrid spatio-temporal data indexing method for trajectory databases.
In recent years, there has been tremendous growth in the field of indoor and outdoor positioning sensors continuously producing huge volumes of trajectory data that has been used in many fields such as location-based services or location intelligence. Trajectory data is massively increased and semantically complicated, which poses a great challenge on spatio-temporal data indexing. This paper proposes a spatio-temporal data indexing method, named HBSTR-tree, which is a hybrid index structure comprising spatio-temporal R-tree, B*-tree and Hash table. To improve the index generation efficiency, rather than directly inserting trajectory points, we group consecutive trajectory points as nodes according to their spatio-temporal semantics and then insert them into spatio-temporal R-tree as leaf nodes. Hash table is used to manage the latest leaf nodes to reduce the frequency of insertion. A new spatio-temporal interval criterion and a new node-choosing sub-algorithm are also proposed to optimize spatio-temporal R-tree structures. In addition, a B*-tree sub-index of leaf nodes is built to query the trajectories of targeted objects efficiently. Furthermore, a database storage scheme based on a NoSQL-type DBMS is also proposed for the purpose of cloud storage. Experimental results prove that HBSTR-tree outperforms TB*-tree in some aspects such as generation efficiency, query performance and query type.


[Surgical vascular anatomy of the thoracic wall].
Since the rediscovery of the latissimus dorsi flap in 1976 axial skin- and musculocutaneous flaps have dramatically improved the possibilities of plastic reconstruction. Better knowledge of the microvascular anatomy of the thoracic wall is the condition for safe flap surgery. The frequent topographic variations and the possibility of a reversed flow through vascular anastomosis are shown. This paper is ment to be a basic introduction to the following communications on flaptechniques in the same journal.


The evolution of postpairing male mate choice.
An increasing number of empirical studies in animals have demonstrated male mate choice. However, little is known about the evolution of postpairing male choice, specifically which occurs by differential allocation of male parental care in response to female signals. We use a population genetic model to examine whether such postpairing male mate choice can evolve when males face a trade-off between parental care and extra-pair copulations (EPCs). Specifically, we assume that males allocate more effort to providing parental care when mated to preferred (signaling) females, but they are then unable to allocate additional effort to seek EPCs. We find that both male preference and female signaling can evolve in this situation, under certain conditions. First, this evolution requires a relatively large difference in parental investment between males mated to preferred versus nonpreferred females. Second, whether male choice and female signaling alleles become fixed in a population versus cycle in their frequencies depends on the additional fecundity benefits from EPCs that are gained by choosy males. Third, less costly female signals enable both signaling and choice alleles to evolve under more relaxed conditions. Our results also provide a new insight into the evolution of sexual conflict over parental care.


Results and complications of CT-guided transthoracic fine-needle aspiration biopsy of pulmonary lesions.
To analyze the cytological findings of CT-guided percutaneous fine-needle aspiration biopsies of the lung, to demonstrate the diagnostic feasibility of the method in the investigation of pulmonary lesions, and to determine the complications of the procedure, evaluating its safety. A retrospective analysis of 89 patients with various types of pulmonary lesions who underwent 97 procedures over a period of five years. The patients were divided into groups regarding the indication for the procedure: suspicion of primary lung cancer (stages IIIB or IV); suspicion of lung cancer (stages I, II, or IIIA) and clinical contraindications for surgery; suspicion of pulmonary metastasis from other organs; and pulmonary lesions with benign radiological aspect. All of the procedures were performed with 25-gauge needles and were guided by spiral CT. The final diagnosis was confirmed by surgical biopsy and clinical/oncological follow-up. For the analysis of complications, the total number of procedures was considered. The main indication for the procedure was suspicion of advanced-stage primary lung cancer. The accuracy of the method for malignant lesions was 91.5%. The lesion was confirmed as cancer in 73% of the patients. The major complication was pneumothorax (27.8%), which required chest tube drainage in 12.4% of the procedures. The principal indication for CT-guided fine-needle biopsy was suspicion of primary lung cancer in patients who were not surgical candidates. The procedure has high diagnostic feasibility for malignant pulmonary diseases. The most prevalent complication was pneumothorax. However, in most cases, chest tube drainage was unnecessary. No deaths were related to the procedure.


New paths to pluripotent stem cells.
Stem cells obtained from early mammalian embryos and the subsequent establishment of self replicating embryonic stem cell lines (ES) provided a legacy resource of pluripotent cells capable of differentiating into specific cell lineages of the adult organism. Still the most versatile source of pluripotent cells, their application to potential human therapeutic use has been encumbered by various technical and ethical objections. New sources of embryonic pluripotent stem cells have been sought, the isolation of ES cell lines from a single blastomere that avoids destruction of the human embryo, the use of arrested embryos no longer capable of completing development or using post-implantation embryos as stem cell providers. The successful cloning and reprogramming of adult animal cell nuclei by somatic cell nuclear transplantation (SCNT) or nuclear transfer (NT) provides stem cells tailored to the donor organism, though a step away for human use. Variations in this procedure are altered SCNT, that would block human use for reproduction and the use of parthenotes to induce pluripotent stem cell lines. All of these NT methods depend upon a very limited supply of healthy oocyte host cells. Enucleated fertilized eggs have been substituted for oocytes and the production of stem cell somatic cell hybrids by cell fusion have potential use for nuclear transfer ES cells not directly dependent on oocytes. Recovery of cells from human amniotic fluid has yielded stem cells that share some pluripotent characteristics but are multipotent stem cells. Adult somatic cells have been reprogrammed recently by retroviral transduction using four transcription factors to induce pluripotent stem cells (iPS) with great promise. Each of these procedures has limitations at present for extensive use in human regenerative medicine.


Pathobiology of hepatitis C.
Hepatitis C virus (HCV) represents the major etiologic agent of non-A, non-B hepatitis. The pathological changes in hepatitis C are characterized by the histologic triad of lymphoid aggregates in portal tracts, epithelial damage of small bile ducts, and micro- and macro-vesicular steatosis. HCV antigens are demonstrable in the cytoplasm of infected hepatocytes by immunohistochemical staining with mono- or polyclonal antibodies, particularly when frozen tissues are employed. Detection of HCV RNA sequences in fixed liver tissues by in situ hybridization appears to be a more sensitive method than immunohistochemical staining. These studies are important to determine the viral load and expression pattern of HCV in the infected liver. The mechanism of hepatocyte and bile duct injury in HCV infection appears to be related to the host immune response to the virus, although direct viral cytopathogenicity may also pay a role.


Association between follow-up blood cultures for gram-negative bacilli bacteremia and length of hospital stay and duration of antibiotic treatment: A propensity score-matched cohort study.
It remains unclear whether a follow-up blood culture (FUBC) for gram-negative bacilli (GNB) bacteremia should be routinely or selectively performed. To evaluate the value of the practice, we analyzed the association between current FUBC practices and length of stay, antibiotic treatment duration, and in-hospital mortality. Retrospective cohort study. The study was conducted in 4 acute-care hospitals in New York City. The study included hospitalized adults with GNB bacteremia between 2017 and 2018. An FUBC was defined as a blood culture performed between 24 hours and 7 days after an initial blood culture positive for GNB. Using propensity scores for FUBCs performed, patients were matched 1:1 for outcome comparison. In total, 376 hospitalized adults with GNB bacteremia met eligibility criteria. Among them, FUBCs were performed in 271 patients (72%). After propensity score matching, we analyzed 87 pairs of patients with and without an FUBC to compare outcomes. The median length of stay was longer among patients with FUBCs than patients without FUBCs (9 days vs 7 days; P = .017). The median duration of antibiotic treatment was also longer among patients with FUBCs than patients without FUBCs (8 vs 6 days; P = .007). No statistically significant difference was observed in in-hospital mortality between patients with and without an FUBC (odds ratio, 0.37; 95% confidence interval, 0.08-1.36). Current FUBC practices for GNB bacteremia were associated with prolonged length of stay and duration of antibiotic treatment. Further data to better inform selectivity criteria for FUBCs in GNB bacteremia are needed.


Composites in Aerospace and Mechanical Engineering.
An important step towards improving performance while reducing weight and maintenance needs is the integration of composite materials into mechanical and aerospace engineering. This subject explores the many aspects of composite application, from basic material characterization to state-of-the-art advances in manufacturing and design processes. The major goal is to present the most recent developments in composite science and technology while highlighting their critical significance in the industrial sector-most notably in the wind energy, automotive, aerospace, and marine domains. The foundation of this investigation is material characterization, which offers insights into the mechanical, chemical, and physical characteristics that determine composite performance. The papers in this collection discuss the difficulties of gaining an in-depth understanding of composites, which is necessary to maximize their overall performance and design. The collection of articles within this topic addresses the challenges of achieving a profound understanding of composites, which is essential for optimizing design and overall functionality. This includes the application of complicated material modeling together with cutting-edge simulation tools that integrate multiscale methods and multiphysics, the creation of novel characterization techniques, and the integration of nanotechnology and additive manufacturing. This topic offers a detailed overview of the current state and future directions of composite research, covering experimental studies, theoretical evaluations, and numerical simulations. This subject provides a platform for interdisciplinary cooperation and creativity in everything from the processing and testing of innovative composite structures to the inspection and repair procedures. In order to support the development of more effective, durable, and sustainable materials for the mechanical and aerospace engineering industries, we seek to promote a greater understanding of composites.


Simulations of Multifocal Vision in Patients With Previous Monofocal Intraocular Lens Implantation.
To evaluate the effectiveness and patient acceptance of multifocal vision simulation in patients with previous monofocal intraocular lens (IOL) implantation, and to explore their willingness-to-pay (WTP) and willingness-to-accept (WTA) based on the perceived advantages and disadvantages of multifocal vision. Seventeen patients with previous monofocal IOL implantation participated in this cross-sectional study. The SimVis Gekko device (2EyesVision SL) was used to simulate monofocal (Evaluation B) and multifocal (Evaluation C) visual experiences, compared to their existing vision (Evaluation A). Visual acuity at three distances and defocus curves were measured. Patients responded to inquiries about visual quality in each evaluation, bothersomeness of photic phenomena, probability to select the visual experience, and the monetary value they associated with enhanced WTP or diminished WTA visual quality. The simulations underestimated the visual acuity reported for the IOL in existing literature by one or two lines, depending on the testing distance. This underestimation was more pronounced in defocus curves. However, 70.6% of patients were likely or very likely to opt for multifocal vision, indicating they perceived the benefits of multifocality. The WTP for multifocal vision was twice that of monofocal vision, and the WTP/WTA ratio exceeded 1, suggesting the perceived vision benefits outweighed potential drawbacks. Despite underestimating the expected postoperative visual performance, the multifocal simulation enabled patients to perceive the benefits of multifocal vision to some extent. This system could be beneficial in avoiding potential postoperative complaints, but the possible rise in false-positive results should be considered and evaluated in future research. [J Refract Surg. 2023;39(12):831-839.].


Hereditary tyrosinemia. Formation of succinylacetone-amino acid adducts.
Succinylacetone (SA) (4,6-dioxoheptanoic acid) is an abnormal metabolite produced in patients with hereditary tyrosinemia as a consequence of an inherited deficiency of fumaryl acetoacetate hydrolase activity. Patients with this disease are associated with a number of abnormalities, including aminoaciduria, proteinuria, liver failure, commonly hepatoma, and decreased GSH concentration in the liver. In the course of our studies of tyrosinemia, we found that the urine of patients with this disorder contains material(s) that absorbs light at 315 nm. We investigated the nature of the 315 nm material in detail. SA was found to react with amino acids and protein nonenzymatically, to form stable adducts at physiological temperature and pH. All SA adducts with amino acids and/or proteins exhibited an absorption peak at 315 nm. Although all amino acids reacted with SA, the most reactive amino acid was lysine (Lys), followed, in order, by glycine, methionine, phenylalanine, serine, alanine, and glutamine. SA-adducts were unstable at pH below 6, while they were made considerably more stable after reduction with NaBH4, suggesting that SA forms an adduct via Schiff base formation. High-performance liquid chromatography (HPLC) analysis of urines from patients with tyrosinemia revealed the existence of SA-glycine, SA-methionine, SA-tyrosine, and SA-phenylalanine. After digestion of urines with proteinase K, three more HPLC peaks appeared, which all corresponded to SA-Lys adducts. TLC analysis of SA-Lys showed that SA-Lys could form as many as seven different adducts. No SA-adduct peaks were observed in HPLC in urines from normal subjects, patients with other forms of aminoaciduria, or patients with the nephrotic syndrome. In addition to amino acids and proteins, SA reacted with reduced glutathione (GSH) and formed a stable adduct. These findings suggest that SA adduct formation with amino acids, GSH, and proteins is a significant process occurring in tyrosinemia, and may account for certain of the pathologic findings in this hereditary disorder.


Search for lepton-flavor violation in the decay tau- --> l- l+ l-.
A search for the lepton-flavor-violating decay of the tau into three charged leptons has been performed using 91.5 fb(-1) of data collected at an e(+)e(-)center-of-mass energy around 10.58 GeV with the BABAR detector at the SLAC storage ring PEP-II. In all six decay modes considered, the numbers of events found in data are compatible with the background expectations. Upper limits on the branching fractions are set in the range (1-3)x10(-7) at 90% confidence level.


Catalytic asymmetric addition of dimethylzinc to alpha-ketoesters, using mandelamides as ligands.
[reaction: see text] A strategy based on the control of the electron-donating capabilities of the coordinating groups of the ligand has been applied in the catalytic asymmetric addition of organometallic reagents to ketoesters. Mandelamides having deprotonated alcohol and carboxyamido groups catalyzed the addition of dimethylzinc to alpha-ketoesters with good yields and ee (up to 90%).


Dipolar repulsion in α-halocarbonyl compounds revisited.
The concept of dipolar repulsion has been widely used to explain several phenomena in organic chemistry, including the conformational preferences of carbonyl compounds. This model, in which atoms and bonds are viewed as point charges and dipole moment vectors, respectively, is however oversimplified. To provide a causal model rooted in quantitative molecular orbital theory, we have analyzed the rotational isomerism of haloacetaldehydes OHC-CH2X (X = F, Cl, Br, I), using relativistic density functional theory. We have found that the overall trend in the rotational energy profiles is set by the combined effects of Pauli repulsion (introducing a barrier around gauche that separates minima at syn and anti), orbital interactions (which can pull the anti minimum towards anticlinal to maximize hyperconjugation), and electrostatic interactions. Only for X = F, not for X = Cl-I, electrostatic interactions push the preference from syn to anti. Our bonding analyses show how this trend is related to the compact nature of F versus the more diffuse nature of the heavier halogens.


Weight regulation, leptin and growth hormone.
Leptin, the product of the adipose tissue-specific ob gene, is a newly recognized hormone involved in the regulation of metabolism and body composition. Leptin appears to provide information to the central nervous system on the amount of energy stored in the adipose tissue. Serum leptin levels are highly correlated with body fat mass in adults, children and newborns. Obese individuals have significantly higher circulating leptin than normal, lean subjects. In addition, females have higher serum leptin than males with equivalent fat mass. Although leptin correlates with fat mass, circulating concentrations are altered by extremes in energy intake, such as fasting and overfeeding. Defects in leptin or its receptor in the hypothalamus lead to the development of obesity in several rodent models; however, no such deleterious defects have been identified in humans to date. Taken together, these observations suggest that humans may be resistant to their endogenous leptin levels. Despite this, studies in rodents demonstrating that leptin administration can cause weight loss in both ob/ob mice, and in normal weight controls suggest that leptin may be useful in the treatment of human obesity. This review will summarize the current understanding of leptin and its role in the regulation of body composition. In addition, the interaction of leptin with other metabolic hormones including growth hormone will be discussed.


Learning a Deep Model for Human Action Recognition from Novel Viewpoints.
Recognizing human actions from unknown and unseen (novel) views is a challenging problem. We propose a Robust Non-Linear Knowledge Transfer Model (R-NKTM) for human action recognition from novel views. The proposed R-NKTM is a deep fully-connected neural network that transfers knowledge of human actions from any unknown view to a shared high-level virtual view by finding a set of non-linear transformations that connects the views. The R-NKTM is learned from 2D projections of dense trajectories of synthetic 3D human models fitted to real motion capture data and generalizes to real videos of human actions. The strength of our technique is that we learn a single R-NKTM for all actions and all viewpoints for knowledge transfer of any real human action video without the need for re-training or fine-tuning the model. Thus, R-NKTM can efficiently scale to incorporate new action classes. R-NKTM is learned with dummy labels and does not require knowledge of the camera viewpoint at any stage. Experiments on three benchmark cross-view human action datasets show that our method outperforms existing state-of-the-art.


Interventions to improve decision making and reduce racial and ethnic disparities in the management of prostate cancer: a systematic review.
Ethnic minorities are disproportionately impacted by prostate cancer (PCa) and are at risk for not receiving informed decision making (IDM). We conducted a systematic literature review on interventions to improve: (1) IDM about PCa in screening-eligible minority men, and (2) quality of life (QOL) in minority PCa survivors. MeSH headings for PCa, ethnic minorities, and interventions were searched in MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, and PsycINFO. SUBJECT ELIGIBILITY CRITERIA: We identified U.S.-based, English-language articles (1985 - 2010) on interventions to improve PCa IDM and QOL that included 50% or more minority patients or analyses stratified by race/ethnicity. Articles (n = 19) were evaluated and scored for quality using a Downs and Black (DB) system. Interventions were organized by those enhancing 1) IDM about PCa screening and 2) improving QOL and symptom among PCa survivors. Outcomes were reported by intervention type (educational seminar, printed material, telephone-based, video and web-based). Fourteen studies evaluated interventions for enhancing IDM about PCa screening and five evaluated programs to improve outcomes for PCa survivors. Knowledge scores were statistically significantly increased in 12 of 13 screening studies that measured knowledge, with ranges of effect varying across intervention types: educational programs (13% - 48% increase), print (11% - 18%), videotape/DVD (16%), and web-based (7% - 20%). In the final screening study, an intervention to improve decision-making about screening increased decisional self-efficacy by 9%. Five cognitive-behavioral interventions improved QOL among minority men being treated for localized PCa through enhancing problem solving and coping skills. Weak study designs, small sample sizes, selection biases, and variation in follow-up intervals across studies. Educational programs were the most effective intervention for improving knowledge among screening-eligible minority men. Cognitive behavioral strategies improved QOL for minority men treated for localized PCa.


Relationship between cell wall, cytoplasmic membrane, and bacterial motility.
High-resolution electron microscopy of polarly flagellated bacteria revealed that their flagella originate at a circular, differentiated portion of the cytoplasmic membrane approximately 25 nm in diameter. The flagella also have discs attaching them to the cell wall. These attachment discs are extremely resistant to lytic damage and are firmly bound to the flagella. The cytoplasm beneath the flagellum contains a granulated basal body about 60 nm in diameter, and a specialized polar membrane. The existence of membrane-bound basal bodies is shown to be an artifact arising from adherence of cell wall and cytoplasmic membrane fragments to flagella in lysed preparations. Based on structures observed, a mechanism to explain bacterial flagellar movement is proposed. Flagella are considered to be anchored to the cell wall and activated by displacement of underlying cytoplasmic membrane to which they are also firmly attached. An explanation for the membrane displacement is given.


A foodborne outbreak of gastroenteritis caused by Norovirus and Bacillus cereus at a university in the Shunyi District of Beijing, China 2018: a retrospective cohort study.
On September 4, 2018, a boarding school in the Shunyi District of Beijing, China reported an outbreak of acute gastroenteritis. At least 209 suspected students caused of diarrhea and vomiting. The case was investigated, and control measures were taken to prevent further spread. A retrospective cohort study was conducted among the school students and staff in order to test hypothesis that high risk of food served at the school canteen. We collected information on demographics, refectory records, person to person transmission by uniform epidemiological questionnaire. Risk ratios (RR) and 95% confidence intervals (CI) were calculated. Stool specimens of cases and canteen employees, retained food, water, and environmental swabs were investigated by laboratory analysis. We identified 209 cases (including 28 laboratory-confirmed cases) which occurred from August 29 to September 10. All cases were students, and the average age was 20, 52% were male. The outbreak lasted for 13 days, and peaked on September 5. Consumption of Drinks stall and Rice flour stall on September 1 (RR:3.4, 95%CI:1.5-7.8, and RR:7.6, 95%CI:2.8-20.2), Rice flour stall and Fish meal stall on September 2 (RR:4.0, 95%CI:1.2-13.6, and RR:4.6, 95%CI:1.7-12.5), muslim meal stall on September 4 (RR:2.7, 95%CI:1.3-5.4), Barbeque stall on September 5 (RR:3.0, 95%CI:1.2-7.0) were independently associated with increased risk of disease within the following 2 days. Among 35 specimens of rectal swabs or feces from students, 28 specimens were positive. Norovirus GI.6 alone was detected in 23 specimens, Bacillus cereus alone in 3 specimens and both norovirus GI.6 and Bacillus cereus in 2 specimens. Ten specimens of rectal swabs from canteen employees were positive for norovirus GI, and 2 specimens were positive for Bacillus cereus. Four retained food specimens were positive for Bacillus cereus, and environmental samples were negative for any viruses or bacteria. Our investigation indicated that canteen employees were infected by two pathogens (norovirus and Bacillus cereus) and transmission may have been possible due to unhygienic practices. Student consumption of food or drink at high-risk stalls was determined as the probable cause of the outbreak.


Eugenol Attenuates Cerebral Ischemia-Reperfusion Injury by Enhancing Autophagy via AMPK-mTOR-P70S6K Pathway.
Eugenol, as an active compound isolated from Acorus gramineus, has been shown to protect against cerebral ischemia-reperfusion (I/R) injury. Nonetheless, the detailed neuroprotective mechanisms of eugenol in cerebral I/R injury have not been elaborated. In the present study, cerebral I/R injury model was established by middle cerebral artery occlusion (MCAO) in rats. HT22 cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) to mimic cerebral I/R injury in vitro. The results showed that eugenol pre-treatment relieved cerebral I/R injury as evidenced by improving neurological deficits and reducing infarct volume. Autophagy was induced by MCAO, which was further promoted by eugenol administration. Moreover, rapamycin, an activator of autophagy, promoted eugenol-induced decreases in neurological score, infarct volume, brain water content, and apoptosis. However, pretreatment with 3-MA, an inhibitor of autophagy, led to the opposite results. Similarly, eugenol pretreatment increased the viability and restrained apoptosis of OGD/R-challenged HT22 cells. OGD/R-induced autophagy was strengthened by eugenol. Mechanically, eugenol promoted autophagy through regulating AMPK/mTOR/P70S6K signaling pathway in vivo and in vitro. In conclusion, pretreatment with eugenol attenuated cerebral I/R injury by inducing autophagy via AMPK/mTOR/P70S6K signaling pathway.


Effectiveness of estradiol and progesterone in inducing LH release in different stages in rat estrous cycles.
The effectiveness of estradiol (E2) and progesterone (P4) in inducing the release of the luteinizing hormone (LH) in the acutely ovariectomized (OVx) rats was studied. Female rats were Ovx in different stages of the estrous cycles and received a series of injections of E2 and P4. LH dynamic changes in the blood were examined in the afternoon of the following day after Ovx. Intact rats treated with oil vehicle or E2 and P4 were used as controls. The surgical operation and oil treatment did not interfere with the normal reproductive rhythm and LH secretion, but treatment with E2 and P4 did facilitate the LH release in some intact rats. E2 and P4 were very effective in inducing LH release in Ovx rats as compared with controls. Results indicated that E2 and P4 are essential substances in eliciting the LH surge, but their efficacies are dependent on the stage in the estrous cycles.